Melatonin (N-acetyl-5-methoxytryptamine, MLT), an indole hormone synthesized primarily in the pineal gland and the retina, controls several essential physiological functions associated with circadian and seasonal rhythms. It is involved in immune responses, aging processes and age-related diseases. Because all these process are associated with oxidative damage of vital cell components, it has been postulated that melatonin may function as a natural antioxidant and free radical scavenger. It has further been suggested that EMF-induced decrease in nocturnal levels of melatonin may be responsible for the weak association between environmental EMF exposure and cancer. The primary objective of this research project was to determine rate constants for the reaction of MLT with free radicals (hydroxyl, methyl, methoxyl) and with singlet oxygen a highly oxidizing form of oxygen. In addition to MLT, we studied related indoles 6-hydroxymelatonin, 6-chloromelatonin, 5-methoxytryptamine, 5-hydroxytryptamine, and a tryptophan metabolite kynurenine.We have found that all the indoles react with the hydroxyl radical at near diffusion controlled rates. The interaction of the indoles with methyl radicals is less efficient. In contrast, scavenging of methoxyl radicals is a very fast process. We found no evidence for a reaction between MLT and superoxide. The singlet oxygen quenching efficacy depends on the position and the nature of the substituent(s) of the indole nucleus, and also on the reaction environment. The melatonin precursor serotonin generated hydroxyl radicals in the presence of ferric iron and hydrogen peroxide, and the melatonin metabolite 6-hydroxymelatonin generated copious amounts of hydroxyl radicals even in the absence of exogenously added hydrogen peroxide. Given the reported low toxicity of MLT, its ready accumulation in all types of cells due to its high lipophilicity and distribution throughout the entire body via the blood stream, melatonin may be considered as a potential antioxidant when taken in pharmacological doses. However, the physiological concentrations of melatonin (100 pg/ml in the plasma) are probably too low for the hormone to act as a physiological antioxidant. Thus it seems highly improbable that the biological effects of EMF can be exerted via a modulation of melatonin levels. - melatonin, indole hormone, pineal gland, retina,hydroxyl radicals